It is known that solar radiation can be harmful to humans. Indeed, most solar energy is emitted as UV rays, which penetrate deeply into the epidermis. The skin protects itself from solar radiation, by synthesizing melanin, a pigment capable of absorbing UV rays and limiting their deep penetration into the dermis. However, the rate of melanin synthesis varies from one individual to another, and filtration is not sufficient to efficiently protect against the sun's photo damage. In particular, UV-B wavelengths (280-320 nm) cause sunburn on sensitive skin, or when skin is frequently exposed to sunlight. Similarly, UVA wavelengths (320-400 nm) are known to induce skin tanning, to accelerate skin aging and to be involved in the development of many skin cancers.
Many studies have been conducted to develop preparations, usually topical, to protect the skin when frequently exposed to sun. These preparations often include carotenoids, known to be used by plants to protect themselves from sun damage. Carotenoids are orange and yellow pigments and are frequently found in many other living organisms. They belong to the chemical family of isoprenoids and are liposoluble. They are synthesized by algae, green plants and many fungi and bacteria (including cyanobacteria). Animals are not able to produce carotenoids and consequently take them up from their food.
Carotenoids are known for their photoprotective activity, related to their absorption of light rays (screen barrier function) and also to their antioxidant properties, which enable them to effectively neutralize peroxyl radicals and singlet oxygen (Sies and Stahl, 1995, 2004). They can be used externally but also internally, because some of the carotenoids ingested by animals accumulate in the skin. Supplementation with β-carotene and lycopene, alone or mixed with other carotenoids, shows a systemic photoprotection, as measured by a decrease in UV-induced erythema.
A randomized cross-over clinical study showed that a mixture of carotenoids reduces oxidative stress. This study describes the effect of carotenoids in 32 individuals who were non-smokers and in good health who daily received for a period of 3 weeks and in cross-over, separated by a washout of 12 weeks 4 capsules containing, either 1 g of fish oil, or 1 g of fish oil supplemented with a mixture of carotenoids (7.6 mg of total carotenoids including 2.9 mg bixin per capsule). It was observed that the carotenoid mixture reduces the oxidative stress induced by fish oil (rich in the polyunsaturated fatty acids 20:5 and 20:6) consumption. This is illustrated by an increased stability of the LDL measured in an ex-vivo oxidation assay and by the reduced concentration of a DNA-damage marker (8-hydroxy-2′-deoxyguanosine) in urine (Kiokias and Gordon, 2003). Another study, performed in mice, showed that an oral administration of various carotenoids, including bixin (200 mg=80 micromoles per kilogram of body weight) before γ-irradiation (1.5-3.0 Gy) reduced the occurrence of chromosomal damage, assessed by the micronucleus test (Thresiamma et al., 1998). Bixin is also able to reduce the side-effects of chemotherapy when orally administered prior to its application (Silva et al., 2001).
The antioxidant activity of norbixin on plasmid DNA was studied by inducing breaks by free-radical hydrogen peroxide H2O2 in the presence of Sn2+ or Fe2+ ions in the Fenton reaction: low concentrations of norbixin (10 μM) protect plasmid DNA in the presence of 10 μM of H2O2 (Kovary et al., 2001). In addition, norbixin increases by a factor of 10 the survival of bacteria (E. coli) when subjected to UV-radiation in the presence of hydrogen peroxide H2O2 or superoxide anion O2.-. The UV-C induced SOS system is reduced by 2.3 times in the presence of norbixin (Júnior et al., 2005). Finally, norbixin has a antimutagenic activity, and reduces by 87% the mutagenic effect of H2O2 on Salmonella typhimurium (Kovary et al., 2001).
More generally, it has been shown in cell-free systems that carotenoids can scavenge superoxide anions generated by the xanthine/xanthine oxidase system. The scavenging ability depends on the carotenoid and decreases in the order of canthaxanthin>bixin>lutein>β-carotene (Corol et al., 2003). For its antioxidant effects, bixin has been proposed to be included in foods (Levy and Levy, 2003).
Based on their properties, liposoluble carotenoids have been included in preparations to be applied to the skin before and during sun exposure in order to protect it from sun damage. Moreover, their pigmenting properties can allow the coloration of the epidermal cells layer in orange, thus accentuating the impression of tanning. A photostable screening cosmetic preparation has been developed to protect human skin against UV-radiation, including a small amount (0.0025 to 0.009% in weight) of bixin in an oily extract mixture (Grollier et al., 1991).
However, carotenoids may also be ingested and play their antioxidant role in the dermal and epidermal cells. The ingested compounds are indeed found in plasma and in various tissues, including skin (Richelle et al., 2006). The human skin contains an average of 0.2 to 0.6 ng/g of total carotenoids, with wide variations between individuals and between areas of the body within the same individual (Stahl and Sies, 2007). Ingestion of food supplemented with carotenoids increases its content in the dermis (Stahl et al., 1998). To be effective, food supplemented in carotenoids must be used for an extended period: longer than 10 weeks (Stahl et al., 2000).
Such an approach has shown its efficacy in several cases: a mixture of 30 to 90 mg/day for 24 weeks of β- and α-carotene (Lee et al., 1999), a tomato extract providing 16 mg/day of lycopene for 12 weeks (Stahl et al., 2001, 2006), an algal extract (Dunaniella salina) providing 24 mg/day of β-carotene, or a mixture (1:1:1) of β-carotene, lutein and lycopene for 12 weeks (Heinrich et al., 2003). The protective effects appear only gradually, and a single dose administration of 120 mg or a daily dose of 90 mg of β-carotene over 23 days is ineffective (Garmyn et al., 1995). However, Kläui et al. (1973) who proposed ingestion of mixtures of carotenoids including possibly bixin for skin protection against UV rays indicate that a treatment starting from 10 to 20 days before exposure to sunlight is sufficient.
Carotenoids are generally considered as low or non-toxic molecules (Agner et al., 2004), even at chronic doses of 3 g/kg in animals (Trumbo, 2005).